Abstract
BackgroundAlthough global malaria mortality is declining, estimates may not reflect better inpatient management of severe malaria (SM) where reported case fatality rates (CFRs) vary from 1–25%.MethodsA meta-analysis of prospective studies of SM was conducted to examine i) whether hypothesized differences between clinical features and outcome in Melanesian compared with African or Asian children really exist, and ii) to explore temporal changes in overall and complication-specific CFRs. The proportions of different SM complications and, overall and complication-specific CFRs were incorporated into the meta-analysis. Adjustments were made for study-level covariates including geographic region, SM definition, artemisinin treatment, median age of participants and time period.FindingsSixty-five studies were included. Substantial heterogeneity (I 2>80%) was demonstrated for most outcomes. SM definition contributed to between-study heterogeneity in proportions of cerebral malaria (CM), metabolic acidosis (MA), severe anemia and overall CFR, whilst geographic region was a significant moderator in for CM and hypoglycemia (HG) rates. Compared with their African counterparts, Melanesian children had lower rates of HG (10% [CI95 7–13%] versus 1% [0–3%], P<0.05), lower overall CFR (2% [0–4%] versus 7% [6–9%], P<0.05) and lower CM-specific CFR (8% [0–17%] versus 19% [16–21%], P<0.05). There was no temporal trend for overall CFR and CM-specific CFR but declining HG- and MA- specific CFRs were observed.InterpretationThese data highlight that recent estimates of declining global malaria mortality are not replicated by improved outcomes for children hospitalized with SM. Significant geographic differences in the complication rates and subsequent CFRs exist and provide the first robust confirmation of lower CFRs in Melanesian children, perhaps due to less frequent HG.
Highlights
Most of the 500 million clinical cases of malaria due Plasmodium falciparum estimated to occur globally are uncomplicated [1], some (1–4%) are considered severe enough to require hospitalization and/or parenteral antimalarial treatment [2]
Asian children have a higher case fatality rates (CFRs) associated with severe anemia than African children
The present analyses show that, in contrast to population studies of malaria-attributable mortality [10], there has been no reduction in overall CFR or cerebral malaria-associated CFR over time despite declining CFRs due to both hypoglycemia and metabolic acidosis
Summary
Most of the 500 million clinical cases of malaria due Plasmodium falciparum estimated to occur globally are uncomplicated [1], some (1–4%) are considered severe enough to require hospitalization and/or parenteral antimalarial treatment [2]. The term ‘severe malaria’ is currently applied when asexual forms of P. falciparum are detected in the peripheral blood and there is impaired consciousness or coma, prostration, multiple seizures, hyperlactatemia or metabolic acidosis, severe anemia, dark urine, hypoglycemia, jaundice, respiratory distress, persistent vomiting, abnormal bleeding, shock, and/or renal failure [3] These clinical criteria reflect the World Health Organization (WHO) 2000 definition of severe malarial illness [3] that is based on descriptive studies of African children and Asian adults with severe P. falciparum infections. It has evolved from previous iterations, published in 1986 [4] and 1990 [5], that were developed to identify patients most at risk of death and to provide standard criteria for research studies [3]. Global malaria mortality is declining, estimates may not reflect better inpatient management of severe malaria (SM) where reported case fatality rates (CFRs) vary from 1–25%
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